There are three serotypes of mammalin reovirus (types 1, 2, 3) defined on the basis of neutralizaion antibodies. These serotypes, when injected into newborn animals, cause different diseases of the central nervous systems. Specifically,, type 3 causes an acute encephalitis with destruction of neuronal tissue, while type 1 causes a less severe and more indolent disease, attacking ependymal cells and resulting in hydrocephalus. Thus, there is a natural polymorphism of CNS diseases produced by these serotypes. By utilizing genetic hybrid clones between serotypes 1 and 3, it is possible to determine which viral gene(s) is (are) responsible for the biologic properties of reovirus. these hybrid clones have been utilized to define the molecular basis for the differiing neurotropism of reovirus. We now propose to determine the role of host cell surface receptors in the pathogenesis of reovirus CNS disease. This will be studied in vitro utilizing neuronal cell cultures and in vivo by testing inbred strains of mice with genetic differences at the major histocompatibility locus. Furthermore, the host immune response to the different reovirus serotypeswill be studied to determine which viral gene products are responsible for eliciting humoral and cell mediated immunity to reovirus and what, it any, is their relation to the viral gene products responsible for the induction of CNS disease. The ability to study the genes and gene products responsible for two different diseases in the central nervous system as well as the host response to the viral infection, offers a previously unavailable avenue for studying the pathogenesis of viral disease.